Chromatin associated proteins encoded by the trithorax and Polycomb group (trxG and PcG) of genes are transcriptional regulators which are required for positive and negative maintenance, respectively, or homeotic gene expression. The human homologue of trithorax (TRX) is the ALL- 1/HRX gene, which has been identified in studies of chromosomal rearrangement associated with acute lymphocytic leukemia, and has been shown to play a similar role to that of TRX in maintaining HOX gene expression in humans. Three tightly linked TRE/PRE modules have been identified within several neighboring regulatory regions of the Ultrabithorax (Ubx) gene, In one such TRE/PRE module C, the TRE and the PRE sequences are closely juxtaposed, but separable. Analysis of the proteins which can associate with Trithorax (TPX) showed that TRX interacts directly with ASH1, also a trxG protein, and that those interacting partners may exist in a putative high molecular weight trxG complex(s), which may be formed at the bxd TREs. In addition, we have found that TRX and ALL-1 interact with SNR1 and INI1, which are the members of the Drosophila and human chromatin remodeling BRM/SWI/SNF complexes. These findings, collectively, demonstrate a possible mechanism for guiding remodeling complexes to their natural target genes via interactions with members of multi-protein trxG complexes found at particular response elements. We will focus on chromatographic fractionation of embryonic nuclear extracts in order to purify a putative TRX-containing multimeric protein complex(es). In addition, we propose a comprehensive analysis of the TRE-containing maintenance modules C and D in the bxd region of Ubx which may be associated with similar primary DNA-binding protein complexes. We will further define the functional properties of each chromosomal maintenance elements with respect to interactions with trxG genes, other than TRX. Once individual TREs are identified in both modules, we will identify primary DNA-binding proteins which are associated with these elements.
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